Calculating binding free energies of host–guest systems using the AMOEBA polarizable force field

David R Bell; Rui Qi; Zhifeng Jing; Jin Yu Xiang; Christopher Mejias; Michael J Schnieders; Jay W Ponder; Pengyu Ren

doi:10.1039/C6CP02509A

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Calculating binding free energies of host–guest systems using the AMOEBA polarizable force field

Journal article

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Calculating binding free energies of host–guest systems using the AMOEBA polarizable force field

David R Bell, Rui Qi, Zhifeng Jing, Jin Yu Xiang, Christopher Mejias, Michael J Schnieders, Jay W Ponder and Pengyu Ren

Physical chemistry chemical physics : PCCP, Vol.18(44), pp.30261-30269

2016

DOI: 10.1039/C6CP02509A

PMCID: PMC5102783

PMID: 27254477

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Abstract

Molecular recognition is of paramount interest in many applications. Here we investigate a series of host–guest systems previously used in the SAMPL4 blind challenge by using molecular simulations and the AMOEBA polarizable force field. The free energy results computed by Bennett's acceptance ratio (BAR) method using the AMOEBA polarizable force field ranked favorably among the entries submitted to the SAMPL4 host–guest competition [Muddana, et al., J. Comput.-Aided Mol. Des., 2014, 28, 305–317]. In this work we conduct an in-depth analysis of the AMOEBA force field host–guest binding thermodynamics by using both BAR and the orthogonal space random walk (OSRW) methods. The binding entropy–enthalpy contributions are analyzed for each host–guest system. For systems of inordinate binding entropy–enthalpy values, we further examine the hydrogen bonding patterns and configurational entropy contribution. The binding mechanism of this series of host–guest systems varies from ligand to ligand, driven by enthalpy and/or entropy changes. Convergence of BAR and OSRW binding free energy methods is discussed. Ultimately, this work illustrates the value of molecular modelling and advanced force fields for the exploration and interpretation of binding thermodynamics.

Details

Title: Subtitle: Calculating binding free energies of host–guest systems using the AMOEBA polarizable force field
Creators: David R Bell - Department of Biomedical Engineering, The University of Texas at Austin, Austin, USA
Rui Qi - Department of Biomedical Engineering, The University of Texas at Austin, Austin, USA
Zhifeng Jing - Department of Biomedical Engineering, The University of Texas at Austin, Austin, USA
Jin Yu Xiang - Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St. Louis, USA
Christopher Mejias - Department of Chemistry, Washington University in Saint Louis, Saint Louis, USA
Michael J Schnieders - Department of Biomedical Engineering and Department of Biochemistry, University of Iowa, Iowa City, USA
Jay W Ponder - Department of Chemistry, Washington University in Saint Louis, Saint Louis, USA
Pengyu Ren - Department of Biomedical Engineering, The University of Texas at Austin, Austin, USA
Resource Type: Journal article
Publication Details: Physical chemistry chemical physics : PCCP, Vol.18(44), pp.30261-30269
DOI: 10.1039/C6CP02509A
PMID: 27254477
PMCID: PMC5102783
NLM abbreviation: Phys Chem Chem Phys
ISSN: 1463-9076
eISSN: 1463-9084
Grant note: DOI: 10.13039/100000001, name: National Science Foundation, award: CHE1152823; DOI: 10.13039/100000002, name: National Institutes of Health, award: GM106137, GM114237
Language: English
Date published: 2016
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Biochemistry and Molecular Biology
Record Identifier: 9984025254502771

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